The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin During Meal Ingestion in Patients With T2D
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Plasma glucose
研究概览
简要总结
Delineation of the role of glucagon-like peptide-1 receptor signalling in the glucose-lowering effect of metformin during meal ingestion in patients with type 2 diabetes.
详细描述
Aim: To evaluate the contribution of metformin-induced GLP-1 secretion on the glucose-lowering effect of metformin in patients with type 2 diabetes treated with metformin for 14 days. Furthermore, the investigators aim to elucidate the mechanisms by which metformin-induced GLP-1 secretion may affect glucose levels in patients with type 2 diabetes.
Fifteen patients with type 2 diabetes treated with lifestyle intervention and/or metformin as the only glucose-lowering drug will be enrolled in the study. The effect of a 14-day metformin treatment course on postprandial glucose tolerance will be examined with and without infusion of the GLP-1 receptor antagonist exendin9-39 in 15 patients with type 2 diabetes.
The double-blinded, placebo-controlled, randomised, cross-over study consists of four study days with concomitant infusions of A) placebo + placebo, B) placebo + exendin9-39, C) metformin + placebo and D) metformin + exendin9-39.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes for at least three months (diagnosed according to the criteria of the World Health Organization (WHO)), with a HbA1c <58 mmol/mol.
- •Caucasian ethnicity
- •Lifestyle intervention and/or metformin monotherapy
- •Normal haemoglobin
- •Age >18 years
- •BMI >23 kg/m2 and <35 kg/m2
- •Informed and written consent
排除标准
- •Liver disease
- •Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
- •Hypo- or hyperphosphataemia
- •Reduced kidney function or nephropathy
- •Treatment with medicine that cannot be paused for 12 hours
- •Intake of antibiotics two months prior to study
- •Hypo- or hypercalcaemia
- •Hypo- and hyperthyroidism
- •Treatment with oral anticoagulants
- •Active or recent malignant disease
- •Any treatment or condition requiring acute or sub-acute medical or surgical intervention
- •Lack of effective birth control in premenopausal women
- •Positive pregnancy test on study days in premenopausal women
- •Pregnancy
- •Women who are breastfeeding
- •Any condition considered incompatible with participation by the investigators
- •If the subjects receive any antibiotic treatment while included in the study they will be excluded
研究组 & 干预措施
Placebo
Placebo, oral tablet in 14 days and in liquid meal.
干预措施: Placebo Oral Tablet (Drug)
Metformin
Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.
干预措施: Metformin (Drug)
Saline
Saline infusion (9mg/mL) on experimental days
干预措施: Saline (Drug)
Exendin(9-39)
Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.
干预措施: Exendin (9-39) (Drug)
结局指标
主要结局
Plasma glucose
时间窗: Minutes 240
The difference between the effect of metformin on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin 9-39.
次要结局
未报告次要终点
研究者
Laura Smidt Hansen
Bachelor of Science
University Hospital, Gentofte, Copenhagen